This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. However, treatments are lacking, particularly for the more common 'dry'form of this disease, which is characterized by progressive atrophy of the macula and loss of visual acuity. The goal of this translational research program is to protect and restore vision in these diseases using cell replacement therapy. We propose to use human embryonic stem cell-derived cell lines to preserve function and to restore photoreceptors and retinal pigment epithelial (RPE) cells in rodent and primate models. Specific Aim 1 is to culture and characterize four cell types: a) forebrain-derived human neural stem cells, b) human neural stem cells modified to secrete specific neuroprotective factors, including glial derived growth factor, c) human Schwann cells, and d) human embryonic stem cells isolated at multiple developmental stages along the photoreceptor lineage. Specific Aim 2 is to transplant these cells to the eyes of rodent models with retinal degenerations to test donor cell survival, evidence of functional and morphological rescue and risk of treatment complications. Specific Aim 3 is to define and optimize the cell delivery procedureand dosage and then evaluate safety and biodistribution in rhesus monkeys. Normal eyes will be studied first, followed by a test of efficacy in our unique rhesus monkey model of age-related macular degeneration. Successful completion of this research will pave the way towards human clinical trials that could have considerable impact on the clinical outcomes for this major blinding condition.